Graduate School of Biotechnology, Kyung Hee University, Yongin 17104, South Korea.
Kyung Hee University Hospital at Gangdong, Seoul 05278, South Korea.
Biochem Biophys Res Commun. 2018 May 23;499(4):960-966. doi: 10.1016/j.bbrc.2018.04.028. Epub 2018 Apr 9.
Preservation of pancreatic β-cells is required for the development of therapies for type 1 and type 2 diabetes (T1D and T2D, respectively). Our previous study demonstrated that substance P (SP) preserves β-cell populations in mice with streptozotocin-induced T1D. Here, we demonstrated that chronic systemic treatment with SP restored the mass of β-cells both in nonobese diabetic (NOD) mice with T1D or db/db mice with T2D. SP delayed the onset of T1D in NOD mice via immune modulation. SP inhibited immune infiltration into islets and the salivary glands of NOD mice. In db/db mice, SP treatment rescued glucose intolerance. Moreover, SP inhibited apoptosis, as well as the activation of pancreatic stellate cells in pancreatic islets of db/db mice. SP downregulated the number of α-smooth muscle actin (α-SMA) expressing cells in db/db pancreatic islets. Cleaved-caspase-3 expression was reduced in islets of SP-treated db/db mice compared to that in the control. Therefore, these results suggested that SP may preserve pancreatic β-cells through immune modulation and protection from the stimulated activation of pancreatic stellate cells and apoptosis in T1D and T2D, respectively.
胰腺 β 细胞的保存对于 1 型和 2 型糖尿病（T1D 和 T2D）的治疗方法的发展是必需的。我们之前的研究表明，P 物质（SP）可保存链脲佐菌素诱导的 1 型糖尿病小鼠的 β 细胞群体。在这里，我们证明慢性全身给予 SP 可恢复 T1D 的非肥胖型糖尿病（NOD）小鼠或 T2D 的 db/db 小鼠的 β-细胞质量。SP 通过免疫调节延迟了 NOD 小鼠 T1D 的发病。SP 抑制了 NOD 小鼠胰岛和唾液腺的免疫浸润。在 db/db 小鼠中，SP 治疗可改善葡萄糖耐量异常。此外，SP 抑制了 db/db 小鼠胰岛中的细胞凋亡和胰腺星状细胞的激活。SP 下调了 db/db 胰岛中表达 α-平滑肌肌动蛋白（α-SMA）的细胞数量。与对照组相比，SP 处理的 db/db 小鼠胰岛中的 cleaved-caspase-3 表达减少。因此，这些结果表明，SP 可能通过免疫调节，分别保护胰腺星状细胞的刺激激活和 T1D 和 T2D 中的细胞凋亡，从而保存胰腺 β 细胞。
